Prevalence and Risk Factors for Human Immunodeficiency Virus (HIV) and Syphilis Infections Among Military Personnel in Sierra Leone.
HIV and syphilis infections are common in military personnel in sub-Saharan Africa, which impact combat preparedness and increase demands on the military health care system. The prevalence of HIV is estimated at 1.5% among the general population (15-49 years of age) of Sierra Leone, and the estimated syphilis prevalence ranged from 1.5% to 5.2% based on regional studies. We examined the prevalence and risk factors for these two common sexually transmitted infections in the Sierra Leone military personnel. This cross-sectional study examined 1157 randomly selected soldiers from the Republic of Sierra Leone Armed Forces in 2013 using computer-assisted personal interviews and rapid testing algorithms. Descriptive statistics and logistic regression models were implemented to identify risk factors for HIV and syphilis separately. The mean age of participants was 38 years, 11.1% were female, and 86.5% were married. The seroprevalence of HIV and syphilis were 3.3% (95% confidence interval [CI]: 2.3%-4.3%) and 7.3% (95% CI: 5.9%-8.8%), respectively. Lower educational attainment in women, multiple sexual partners, unintended sex after alcohol use and use of condoms were independently associated with HIV status (p<0.05). After adjustment, HIV infection was associated with female gender, unintended sex after alcohol use, condom use at last sex, having multiple sexual partnerships in the same week and HIV testing outside of military facilities (p<0.05). Increasing age, positive HIV status and rural regions of residence were associated with syphilis seropositivity. The prevalence of sexually transmitted infections among military personnel was higher than the general population of Sierra Leone. Several high-risk sexual behaviors that expose soldiers to HIV and syphilis could be addressed through prevention interventions.


Y not a dead end: epistatic interactions between Y-linked regulatory polymorphisms and genetic background affect global gene expression in Drosophila melanogaster.
The Y chromosome, inherited without meiotic recombination from father to son, carries relatively few genes in most species. This is consistent with predictions from evolutionary theory that nonrecombining chromosomes lack variation and degenerate rapidly. However, recent work has suggested a dynamic role for the Y chromosome in gene regulation, a finding with important implications for spermatogenesis and male fitness. We studied Y chromosomes from two populations of Drosophila melanogaster that had previously been shown to have major effects on the thermal tolerance of spermatogenesis. We show that these Y chromosomes differentially modify the expression of hundreds of autosomal and X-linked genes. Genes showing Y-linked regulatory variation (YRV) also show an association with immune response and pheromone detection. Indeed, genes located proximal to the euchromatin-heterochromatin boundary of the X chromosome appear particularly responsive to Y-linked variation, including a substantial number of odorant-binding genes. Furthermore, the data show significant regulatory interactions between the Y chromosome and the genetic background of autosomes and X chromosome. Altogether, our findings support the view that interpopulation, Y-linked regulatory polymorphisms can differentially modulate the expression of many genes important to male fitness, and they also point to complex interactions between the Y chromosome and genetic background affecting global gene expression.


Biomarkers: background, classification and guidelines for applications in nutritional epidemiology.
One of the main problems in nutritional epidemiology is to assess food intake as well as nutrient/food component intake to a high level of validity and reliability. To help in this process, the need to have good biomarkers that more objectively allow us to evaluate the diet consumed in a more standardized, valid and precise way has often been commented upon. There are various definitions of biomarkers and also different classifications of the same. In general a biomarker can be defined as a characteristic that can objectively measure different biological samples and that can be evaluated as an exposure marker of normal or pathogenic biological processes or of responses to a certain intervention. The biological samples most commonly used in nutritional epidemiology are blood, red blood cells, plasma, serum, urine, nails, saliva, faeces and samples of different tissues. Exposure biomarkers (dietary intake), biomarkers of effects and biomarkers of disease status can be determined from these samples. In turn, exposure biomarkers can be temporarily categorized into markers of acute, medium term or chronic effects. Many difficulties arise in identifying good biomarkers. Currently, advances in omics are opening up new possibilities for obtaining new biomarkers of various kinds, using genomics, epigenomics, transcriptomics, lipidomics, proteomics and metabolomics. We shall review the present situation of biomarkers in nutritional epidemiology as well as the future trends of the new omic biomarkers.


A youth-focused case management intervention to engage and retain young gay men of color in HIV care.
HIV-positive Latino and African-American young men who have sex with men (YMSM) have low rates of engagement and retention in HIV care. An evaluation of a youth-focused case management intervention (YCM) designed to improve retention in HIV care is presented. HIV-positive Latino and African-American YMSM, ages 18-24, who were newly diagnosed with HIV or in intermittent HIV care, were enrolled into a psychosocial case management intervention administered by Bachelor-level peer case managers at two HIV clinics in Los Angeles County, California. Participants met weekly with a case manager for the first two months and monthly for the next 22 months. Retention in HIV primary care at three and six months of follow-up was evaluated as were factors associated with retention in care. From April 2006 to April 2009, 61 HIV-positive participants were enrolled into the intervention (54% African-American, 46% Latino; mean age 21 years). At the time of enrollment into the intervention, 78% of the YMSM had a critical or immediate need for stable housing, nutrition support, substance abuse treatment, or mental health services. Among intervention participants (n=61), 90% were retained in primary HIV care at three months and 70% at six months. Among those who had previously been in intermittent care (n=33), the proportion attending all HIV primary care visits in the previous six months increased from 7% to 73% following participation in the intervention (p<0.0001). Retention in HIV care at six months was associated with increased number of intervention visits (p=0.05), more hours in the intervention (p=0.02), and prescription of HAART. These data highlight the critical needs of HIV-positive African-American and Latino YMSM and demonstrate that a clinic-based YCM can be effective in stabilizing hard-to-reach clients and retaining them in consistent HIV care.


Direct evidence of phospholipids in gecko footprints and spatula-substrate contact interface detected using surface-sensitive spectroscopy.
Observers ranging from Aristotle to young children have long marvelled at the ability of geckos to cling to walls and ceilings. Detailed studies have revealed that geckos are 'sticky' without the use of glue or suction devices. Instead, a gecko's stickiness derives from van der Waals interactions between proteinaceous hairs called setae and substrate. Here, we present surprising evidence that although geckos do not use glue, a residue is transferred on surfaces as they walk-geckos leave footprints. Using matrix-free nano-assisted laser desorption-ionization mass spectrometry, we identified the residue as phospholipids with phosphocholine head groups. Moreover, interface-sensitive sum-frequency generation spectroscopy revealed predominantly hydrophobic methyl and methylene groups and the complete absence of water at the contact interface between a gecko toe pad and the substrate. The presence of lipids has never been considered in current models of gecko adhesion. Our analysis of gecko footprints and the toe pad-substrate interface has significant consequences for models of gecko adhesion and by extension, the design of synthetic mimics.


Managing open loop water resource value chain through IoT focused decision and information integration (DII) modelling using fuzzy MCDM approach.
Water is a limited and invaluable resource that is essential for human survival. Negligence and unregulated water use have brought about a global water crisis. Proper management with a relevant decision and information integration approach can aid water to continue as a renewable resource. The water and wastewater industry must shift from outmoded, inefficient techniques to more sustainable, data-driven solutions to address water concerns and improve public health. The Internet of Things (IoT) has emerged as an innovative strategy for decision and information integration to drive an open-loop Water Value Chain (WVC) efficiently. The IoT-driven network allows objects to connect and communicate, gather data in real-time, analyze data and develop reasonable decision - making insights instantaneously. This study aims to find the enablers of IoT for an open-loop WVC. It examines 25 factors for IoT implementation in the open-loop WVC. The 25 factors are clustered into seven enablers using Principal Component Analysis (PCA). These principal components are analyzed by employing a Multi-Criteria Decision Making (MCDM) approach, i.e., the Fuzzy Decision-Making Trial and Evaluation Laboratory (DEMATEL), which helps to find the cause-effect relationship to prioritize the enablers. The fuzzy set theory is used to address the uncertainty and vagueness in experts' opinions and data deficiency problems. The study reveals that the Ecosystem of an IoT network, IoT network configuration and adaptation and data mobility in an IoT network are the most prominent enablers to consider for the implementation of IoT in an open loop WVC. The study may be helpful for regulatory agencies and enterprises in water distribution and processing for identifying and prioritizing the potential enablers of IoT in an open-loop WVC.


Adolescent gambling on the internet: a review.
Internet gambling is a relatively under-researched area. While our current knowledge remains in its infancy and the prevalence rates are relatively low, researchers and clinicians are predicting greater involvement among youth. A comprehensive search of the relevant literature was undertaken. The resulting relevant literature was classified into four areas. These were (a) the empirical studies on adolescent internet gambling, (b) online gambling-like experiences in adolescence, (c) adolescent gambling via social networking sites, and (d) adolescent gambling via online penny auction sites. Age verification in relation to prevention and regulation is also examined. It is concluded that young people appear to be very proficient in using and accessing new media and are likely to be increasingly exposed to remote gambling opportunities. These young people will therefore require education and guidance to enable them to cope with the challenges of convenience gambling in all its guises.


Temperature-induced formation and contraction of micelle-like aggregates in aqueous solutions of thermoresponsive short-chain copolymers.
A combination of turbidity, light scattering, and steady shear viscosity experiments has revealed that aqueous solutions of an amphiphilic diblock copolymer or a negatively charged triblock copolymer, both containing poly(N-isopropylacrylamide), can undergo a temperature-induced transition from loose intermicellar clusters to collapsed core-shell nanostructures. Turbidity, light scattering, and viscosity results of these short-chain copolymers disclose transition peaks at intermediate temperatures. At high temperatures, the compact core-shell particles from the diblock copolymer aggregate, whereas no renewed interpolymer association is observed for the triblock copolymer or for the solution of the diblock copolymer with added sodium dodecyl sulfate because the electrostatic repulsive interactions suppress the tendency of forming interpolymer clusters. The temperature-induced building up of intermicellar structures and the formation of large aggregates at high temperature in the solution of the diblock copolymer is significantly reduced under the influence of high shear rates.


Skeletal assessment with finite element analysis: relevance, pitfalls and interpretation.
Finite element models simulate the mechanical response of bone under load, enabling noninvasive assessment of strength. Models generated from quantitative computed tomography (QCT) incorporate the geometry and spatial distribution of bone mineral density (BMD) to simulate physiological and traumatic loads as well as orthopaedic implant behaviour. The present review discusses the current strengths and weakness of finite element models for application to skeletal biomechanics. In cadaver studies, finite element models provide better estimations of strength compared to BMD. Data from clinical studies are encouraging; however, the superiority of finite element models over BMD measures for fracture prediction has not been shown conclusively, and may be sex and site dependent. Therapeutic effects on bone strength are larger than for BMD; however, model validation has only been performed on untreated bone. High-resolution modalities and novel image processing methods may enhance the structural representation and predictive ability. Despite extensive use of finite element models to study orthopaedic implant stability, accurate simulation of the bone-implant interface and fracture progression remains a significant challenge. Skeletal finite element models provide noninvasive assessments of strength and implant stability. Improved structural representation and implant surface interaction may enable more accurate models of fragility in the future.


Suppression of colorectal cancer cell growth by combined treatment of 6-gingerol and γ-tocotrienol via alteration of multiple signalling pathways.
Our previous study reported that combined treatment of γ-tocotrienol with 6-gingerol showed promising anticancer effects by synergistically inhibiting proliferation of human colorectal cancer cell lines. This study aimed to identify and elucidate molecular mechanisms involved in the suppression of SW837 colorectal cancer cells modulated by combined treatment of γ-tocotrienol and 6-gingerol. Total RNA from both untreated and treated cells was prepared for transcriptome analysis using RNA sequencing techniques. We performed high-throughput sequencing at approximately 30-60 million coverage on both untreated and 6G + γT3-treated cells. The results showed that cancer-specific differential gene expression occurred and functional enrichment pathway analysis suggested that more than one pathway was modulated in 6G + γT3-treated cells. Combined treatment with 6G + γT3 augmented its chemotherapeutic effect by interfering with the cell cycle process, downregulating the Wnt signalling pathway and inducing apoptosis mainly through caspase-independent programmed cell death through mitochondrial dysfunction, activation of ER-UPR, disruption of DNA repair mechanisms and inactivation of the cell cycle process through the downregulation of main genes in proliferation such as FOXM1 and its downstream genes. The combined treatment exerted its cytotoxic effect through upregulation of genes in stress response activation and cytostatic effects demonstrated by downregulation of main regulator genes in the cell cycle. Selected genes involved in particular pathways including ATF6, DDIT3, GADD34, FOXM1, CDK1 and p21 displayed concordant patterns of gene expression between RNA sequencing and RT-qPCR. This study provides new insights into combined treatment with bioactive compounds not only in terms of its pleiotropic effects that enhance multiple pathways but also specific target genes that could be exploited for therapeutic purposes, especially in suppressing cancer cell growth.


Early expression of the gene for interphotoreceptor retinol-binding protein during photoreceptor differentiation suggests a critical role for the interphotoreceptor matrix in retinal development.
Interphotoreceptor retinol-binding protein (IRBP), the major protein component of the subretinal space, is in a strategic position to mediate cellular interactions between the retinal pigmented epithelium (RPE) and the neural retina. While IRBP appears to be involved in vitamin A transport during the visual cycle in the adult, the role of this protein during eye development has not been determined. As a first step to understanding the role of IRBP during retinal development, we have studied the expression of the mRNA for this glycolipoprotein during photoreceptor differentiation in the rat. A rat neural retina cDNA library was prepared from which an IRBP clone was isolated. The clone contains an open reading frame followed by a 3' noncoding sequence ending in 10 adenosine residues. The coding region has an identity of 83.9 and 82.5% with the nucleotide sequence of human and bovine IRBP, respectively. Rats (Sprague-Dawley, Wistar, and Royal College of Surgeon pink-eyed controls) have a 6.4 and a 5.2-kb mRNA for IRBP which are present in a 1:4 ratio and thus are the only vertebrate known to definitely have more than one major form of the IRBP message. Genomic Southern blots are consistent with the hypothesis that there is only one allele of the IRBP gene, suggesting that the two forms are produced by alternative processing of the mRNA. To generate an antisense RNA probe for use in molecular titration assays and Northern blots, an Eco RI-Bam HI fragment from the coding region was subcloned in between flanking Sp6 and T7 promoters. Total RNA was prepared from undissected rat globes from postnatal days p0-p22. The expression of the mRNA for IRBP was studied by Northern blots and the level of the transcripts determined by solution hybridization assays. Approximately 10(5) IRBP mRNA transcripts/micrograms total eye RNA are present at birth. This increases to a final level of 3.1 X 10(6) transcripts/micrograms total RNA by p9. The one-half maximal level of the mRNA occurs at p4.2 which is 2 wk before the one-half maximal level of IRBP is reached in the subretinal space (Gonzalez-Fernandez, F., R. A. Landers, P. A. Glazebrook, S.-L. Fong, G. I. Liou, D. M. K. Lam, and C. D. B. Bridges. 1984. J. Cell Biol. 99:2092-2098). The expression of the mRNA for IRBP reflects the developmental emergence of the interphotoreceptor matrix as an important structure within the retina.(ABSTRACT TRUNCATED AT 400 WORDS)


Therapeutic efficacy of vincamine in dementia.
This trial was performed to investigate the therapeutic efficacy of vincamine in the treatment of primary degenerative and vascular dementia. 152 male and female patients aged between 50 and 85 years from two psychogeriatric centers and two nursing homes were initially included in the trial and screened for eligibility. 142 patients completed the trial. Clinical diagnosis was established according to DSM-III-R criteria. Allocation of the patients to the primary degenerative dementia of the Alzheimer type (DAT) group or the multi-infarct dementia (MID) group was based on computed tomography scans, electroencephalographic findings and the Hachinski Ischemic Score. In a 12-week double-blind treatment either 30 mg vincamine or placebo was given twice daily. Confirmatory statistics included item 2 of the Clinical Global Impression (CGI), the total score of the Sandoz Clinical Assessment Geriatric (SCAG) scale, the subscale 'need for help' of the nurse's rating of geriatric patients (Beurteilungsskala für geriatrische Patienten; BGP) and the total score of the Short Cognitive Performance Test (Syndrom-Kurztest; SKT). In addition, data on tolerance and on therapy response were evaluated based on descriptive statistics. The therapeutic efficacy of vincamine was clearly demonstrated by confirmatory analysis as the drug was statistically significantly superior to placebo in all four target variables. The clinical relevance of the outcome was further underlined by the results of the responder analysis of the variables SCAG, BGP and SKT. Based on the results of this trial, it can be accepted that the therapeutic effect of vincamine is superior to placebo in patients with mild to moderate dementia of degenerative and vascular etiologies.


Acceptability of a community-embedded intervention for improving adolescent sexual and reproductive health in south-east Nigeria: A qualitative study.
Adolescents have limited access to quality sexual and reproductive health (SRH) services that are key to healthy sexual lives in many low and middle-income countries such as Nigeria. Hence, context-specific interventions are required to increase adolescents' access to and utilisation of SRH. This paper provides new knowledge on the acceptability of a community-embedded intervention to improve access to SRH information and services for adolescents in Ebonyi state, southeast Nigeria. A community-embedded intervention was implemented for six months in selected communities. Thereafter the intervention was assessed for its acceptability using a total of 30 in-depth interviews and 18 focus group discussions conducted with policymakers, health service providers, school teachers, community gatekeepers, parents and adolescents who were purposively selected as relevant stakeholders on adolescent SRH. The interview transcripts were coded in NVivo 12 using a coding framework structured according to four key constructs of the theoretical framework for acceptability (TFA): affective attitude, intervention coherence, perceived effectiveness, and self-efficacy. The outputs of the coded transcripts were analysed, and the emergent themes from each of the four constructs of the TFA were identified. The intervention was acceptable to the stakeholders, from the findings of its positive effects, appropriateness, and positive impact on sexual behaviour. Policymakers were happy to be included in collaborating with multiple stakeholders to co-create multi-faceted interventions relevant to their work (positive affective attitude). The stakeholders understood how the interventions work and perceived them as appropriate at individual and community levels, with adequate and non-complex tools adaptable to different levels of stakeholders (intervention coherence). The intervention promoted mutualistic relations across stakeholders and sectors, including creating multiple platforms to reach the target audience, positive change in sexual behaviour, and cross-learning among policymakers, community gatekeepers, service providers, and adolescents (intervention effectiveness), which empowered them to have the confidence to provide and access SRH information and services (self-efficacy). Community-embedded interventions were acceptable as strong mechanisms for improving adolescents' access to SRH in the communities. Policymakers should promote the community-embedded strategy for holistic health promotion of adolescents.


Disease, Scapegoating, and Social Contexts: Examining Social Contexts of the Support for Racist Naming of COVID-19 on Twitter.
In early 2020, when COVID-19 began to spread in the United States, many Twitter users called it the "Chinese virus," blaming racial outgroups for the pandemic. I collected tweets containing the "Chinese virus" derivatives posted from March to August 2020 by users within the United States and created a data set with 141,290 tweets published by 50,695 users. I calculated the ratio of users who supported the racist naming of COVID-19 per county and merged Twitter data with the county-level census. Multilevel regression models show that counties with higher COVID-19 mortality or infection rates have more support for the racist naming. Second, the mortality and infection rates effects are stronger in counties with faster minority growth. Moreover, it is mainly in poor counties that minority growth enlarges the effects of infection and mortality rates. These findings relate to the theories on disease-induced xenophobia and the debate between conflict and contact theories.


Iterative solutions to the steady-state density matrix for optomechanical systems.
We present a sparse matrix permutation from graph theory that gives stable incomplete lower-upper preconditioners necessary for iterative solutions to the steady-state density matrix for quantum optomechanical systems. This reordering is efficient, adding little overhead to the computation, and results in a marked reduction in both memory and runtime requirements compared to other solution methods, with performance gains increasing with system size. Either of these benchmarks can be tuned via the preconditioner accuracy and solution tolerance. This reordering optimizes the condition number of the approximate inverse and is the only method found to be stable at large Hilbert space dimensions. This allows for steady-state solutions to otherwise intractable quantum optomechanical systems.


A genetic algorithm using hyper-quadtrees for low-dimensional K-means clustering.
The k-means algorithm is widely used for clustering because of its computational efficiency. Given n points in d-dimensional space and the number of desired clusters k, k-means seeks a set of k cluster centers so as to minimize the sum of the squared Euclidean distance between each point and its nearest cluster center. However, the algorithm is very sensitive to the initial selection of centers and is likely to converge to partitions that are significantly inferior to the global optimum. We present a genetic algorithm (GA) for evolving centers in the k-means algorithm that simultaneously identifies good partitions for a range of values around a specified k. The set of centers is represented using a hyper-quadtree constructed on the data. This representation is exploited in our GA to generate an initial population of good centers and to support a novel crossover operation that selectively passes good subsets of neighboring centers from parents to offspring by swapping subtrees. Experimental results indicate that our GA finds the global optimum for data sets with known optima and finds good solutions for large simulated data sets.


Do People Prefer to Pass Along Good or Bad News? Valence and Relevance of News as Predictors of Transmission Propensity
Anecdotal evidence seems to indicate that exaggeratedly bad news may propagate in the marketplace of ideas. Three studies investigate whether people prefer to pass along pieces of bad news or good news that are equated for "surprisingness." People typically prefer to pass along central rather than extreme information (i.e., news that is less surprising rather than more surprising). However, when confronted with extreme information, the results support a preference for congruence, that is, people prefer to pass along news that is congruent with the emotional valence of the domain in question. This means that in emotionally negative domains, contrary to some theoretical predictions, people are willing to pass along bad news even when it is exaggeratedly bad. At the same time, however, people transmit exaggeratedly good news in emotionally positive domains. The general discussion indicates how these results may inform research on word of mouth for consumer products and social relations in organizations.


[The characteristics of the DIC syndrome in gastrointestinal hemorrhages].
With the purpose of assessing the part DIC syndrome has in hemorrhage, blood coagulation system was studied in patients presenting with gastrointestinal hemorrhage. Thrombin, a blood coagulation IIa factor, which is one of the chief markers of DIC syndrome, has been found in great amounts in blood in 50% of cases. But this did not lead to disseminated transformation of fibrinogen to fibrin because of the action of the inhibitor of coagulation during the stage of activation of fibrinogen by thrombin. Antithrombin III had but a minor part in these processes. It is suggested that rise in concentration of thrombin that is not accompanied by formation of disseminated fibrin might be of compensatory and adaptive significance. Another characteristic of blood coagulation system in the patients is depressed plasminolysis, while increase, against this background, in concentration of products of fibrin/fibrinogen degradation that is most common, reflects disturbance in the processes of their elimination from the bloodstream.


A qualitative study of the promotion of exclusive breastfeeding by health professionals in Niamey, Niger.
The practice of exclusive breastfeeding depends on various factors related to both mothers and their environment, including the services delivered by health professionals. It is known that support and counseling by health professionals can improve rates, early initiation and total duration of breastfeeding, particularly exclusive breastfeeding. Mothers' decisions are influenced by health professionals' advice. However, in Niger the practice of exclusive breastfeeding is almost non-existent.The purpose of this exploratory study, of which some results are presented here, was to document health professionals' attitudes and practices with regard to exclusive breastfeeding promotion in hospital settings in the urban community of Niamey, Niger. Fieldwork was conducted in Niamey, Niger. A qualitative approach was employed. Health professionals' practices were observed in a sample of frontline public healthcare facilities. The field observation results presented here indicate that exclusive breastfeeding is not promoted in healthcare facilities because the health professionals do not encourage it and their practices are inappropriate. Some still have limited knowledge or are misinformed about this practice or do not believe in it. They do not systematically discuss exclusive breastfeeding with mothers, or they mention it only briefly and without giving any explanation. Worse still, some encourage the use of breast milk substitutes, which are frequently promoted in healthcare facilities. Thus mothers often receive contradictory messages. The results suggest the need to train or retrain health professionals with regard to exclusive breastfeeding, and regularly supervise their activities.


DNA metabarcoding reveals spatial and temporal variation of fish eye fluke communities in lake ecosystems.
Eye flukes (Diplostomidae) are diverse and abundant trematode parasites that form multi-species communities in fish with negative effects on host fitness and survival. However, the environmental factors and host-related characteristics that determine species diversity, composition, and coexistence in such communities remain poorly understood. Here, we developed a cost-effective cox1 region-specific DNA metabarcoding approach to characterize parasitic diplostomid communities in two common fish species (Eurasian perch and common roach) collected from seven temperate lakes in Estonia. We found considerable inter- and intra-lake, as well as inter-host species, variation in diplostomid communities. Sympatric host species characterization revealed that parasite communities were typically more diverse in roach than perch. Additionally, we detected five positive and two negative diplostomid species associations in roach, whereas only a single negative association was observed in perch. These results indicate that diplostomid communities in temperate lakes are complex and dynamic systems exhibiting both spatial and temporal heterogeneity. They are influenced by various environmental factors and by host-parasite and inter-parasite interactions. We expect that the described methodology facilitates ecological and biodiversity research of diplostomid parasites. It is also adaptable to other parasite groups where it could serve to improve current understanding of diversity, distribution, and interspecies interactions of other understudied taxa.


Endoscope-Assisted Resection of Extra-Axial Premedullary Neurenteric Cyst via Far Lateral-Supracondylar Approach: 2-Dimensional Operative Video.
Neurenteric cysts are rare congenital lesions that may compress the ventral brainstem.1-9 In this operative video, we illustrate the surgical treatment of an intradural extra-axial neurenteric cyst extending from the lower pons to the craniocervical junction. The patient, an asymptomatic 52-yr-old female, underwent surveillance imaging of the premedullary lesion for 14 yr without progression. However, after developing progressive strain-induced headaches, imaging revealed a significant enlargement of the lesion with brainstem compression and partial obstruction of the foramen magnum. Therefore, surgical resection was pursued. The patient consented to the procedure. The patient underwent a lateral suboccipital craniotomy and C1 laminectomy through a far lateral approach. The lesion was immediately visualized upon opening the dura. After identifying the cranial nerves, we resected the tumor while taking care to preserve the neurovascular elements of the cerebellopontine angle and foramen magnum. During the resection, we unexpectedly encountered a firm nodule that was adherent to the right posterior inferior cerebellar artery. This was meticulously dissected and removed en bloc using intraoperative indocyanine green (ICG) angiography. The cavity was inspected with 0-degree and 30-degree endoscopes to ensure complete resection of the lesion. Gross total resection was confirmed on postoperative magnetic resonance imaging. The patient was neurologically intact with no cranial nerve abnormalities and discharged home on postoperative day 3. This case demonstrates that the far lateral-supracondylar approach affords safe access to the ventral pontomedullary and craniocervical junctions and that intraoperative adjuncts, including ICG angiography and endoscopic visualization, can facilitate complete lesion resection with excellent clinical outcomes.


Evaluation of reporting based on descriptional knowledge.
In an attempt to enhance the completeness and clarity of clinical narratives, the authors developed a general formalism for the entry of structured data. The objective of this study was to gain insight into the expressive power of the formalism through its use for reporting in endoscopy. Each of ten endoscopists reported twice about eight endoscopy videotapes. They produced free-text reports first, and then structured reports using this formalism. Statements in the resulting reports were compared. In total, 6.8% of the endoscopists' statements could not be expressed in structured options. Most of these statements were not due to limitations of the formalism itself. Topics mentioned in the free-text reports were described more frequently in the structured reports and, in addition, the structured reports included a greater variety of topics. Overall, increases of 83% for topics not related to abnormal findings (366 in free-text reports and 671 in structured reports) and 45% for features of abnormal findings (406 in free-text reports and 586 in structured reports) were observed. Although there was an overall information gain, features of abnormal findings were, on average, described by only half of the endoscopists. The expressive power of this formalism is promising, but general, multipurpose usage of the acquired data requires that topics be described by a larger percentage of physicians. Since this formalism led to more complete and more uniform data, additional research is justified to study how spontaneous reporting can be augmented further. The few subjects that occurred less often in structured reports suggest a possible negligence effect of structured reporting.


Clinical validation of a new algorithm for computerized dosing of vitamin K antagonist therapy: a retrospective simulation study.
The number of patients on oral anticoagulant therapy has increased in recent years, and this trend is expected to continue. The increased workload for physicians has led to the development of computerized systems to make organizational workflow more efficient. These programs may include algorithms to propose a weekly dosage and timing for the following visit. Before introducing a new algorithm in clinical practice, its safety and efficacy must be validated. We undertook a retrospective simulation study to test a new algorithm for the TAOnet system. The main outcome was the percentage of concordant and discordant proposals between manual- and algorithm-based prescriptions. Pairs of computerized and physician prescriptions were assessed. They were categorized as 0.1-5, 5.1-10 and >10% if the dose was different, and assigned as "algorithm better" or "manual better" dependent upon the subsequent international normalized ratio value. In 61.0% of cases, the manual and computerized weekly dosage assignments were identical; in 15.3% of cases, the difference was between 0.1 and 5%; in 14.7 of cases, it was between 5.1 and 10%; and in 9.0% of cases, it was >10%. The algorithm did better in 43.9% of discordant pairs, generally due to less frequent under-dosing. In conclusion, the new algorithm proved to consistently overlap with the manual method. The algorithm is useful but must be tested in a multi-center, prospective, interventional study.


A Murine Model of a Burn Wound Reconstructed with an Allogeneic Skin Graft.
Trivial superficial wounds heal without complications by primary intention. Deep wounds, such as full thickness burns, heal by secondary intention and require surgical debridement and skin grafting. Successful integration of the donor graft into a recipient wound bed depends on timely recruitment of immune cells, robust angiogenic response and new extracellular matrix formation. The development of novel therapeutic agents, which target some key processes involved in wound healing, are hindered by the lack of reliable preclinical models with optimized objective assessment of wound closure. Here, we describe an inexpensive and reproducible model of experimental full thickness burn wound reconstructed with an allogeneic skin graft. The wound is induced on the dorsum surface of anaesthetized inbred wild type mice from the BALB/C and SKH1-Hrhr backgrounds. The burn is produced using a brass template measuring 10 mm in diameter, which is preheated to 80 °C and delivered at a constant pressure for 20 s. Burn eschar is excised 24 hours after the injury and replaced with a full thickness graft harvested from the tail of a genetically similar donor mouse. No specialized equipment is required for the procedure and surgical techniques are straightforward to follow. The method may be effortlessly implemented and reproduced in most research settings. Certain limitations are associated with the model. Due to technical difficulties, the harvest of thinner split thickness skin grafts is not possible. The surgical method we describe here allows for the reconstruction of burn wounds using full thickness skin grafts. It may be used to carry out preclinical therapeutic testing.


Induction of human gamma interferon by structurally defined polypeptide fragments of group A streptococcal M protein.
The presence of interferon (IFN) has been demonstrated previously (i) in fluids obtained from the middle ears of children with Streptococcus pneumoniae infections, (ii) from the serum of mice injected intraperitoneally with either S. pneumoniae or Streptococcus pyogenes, and (iii) from human lymphoid cell cultures treated with a variety of bacteria. In this study, we showed that highly purified peptic extracts of three different serotypes of group A streptococcal M protein (pep M5, pep M6, and pep M24) stimulated human peripheral leukocytes to produce IFN. IFN production was apparent by 10 h and peaked 24 h after exposure. Dose-response experiments indicated that IFN could be detected in cultures treated with concentrations of M protein as low as 6 micrograms/ml, whereas maximum IFN production occurred at a concentration of 200 micrograms/ml. The IFN had antigenic and physicochemical characteristics of IFN-gamma. Preliminary leukocyte fractionation studies revealed that the IFN-producing cell was a nonadherent lymphocyte with receptors for sheep erythrocytes (T cell). Rabbit antisera specific for these structurally defined polypeptide fragments of streptococcal M protein (pep M5, pep M6, and pep M24) blocked IFN induction by each of the polypeptides. The data suggest that the different serotypes of streptococcal M protein may induce IFN by a common structural determinant shared by each of the polypeptide fragments tested.


Anterior cervical fusion using homologous bone grafts: a comparative study.
A comparative sutyd of homologous and autogenous bone grafts in Smith-Robinson type anterior cervical fusions reveals no significant difference between the two in clinical or radiographic results and no complications related to the use of the homologous grafts from the tissue bank.


Relationships between chronotropic effect, 1-3H-noradrenaline uptake and tissue concentrations of desipramine, protripyline and doxepin in rat isolated atria.
The pharmacological effects of three tricyclic antidepressant agents (desipramine, protriptyline and doxepin) are evaluated in rat isolated atria in relation to their accumulation and efflux kinetics. The pharmacological effects studed are: inhibition of 1-3H-noradrenaline uptake, potentiation of 1-noradrenaline chronotropic response, and changes in spontaneous atrial rate. All drugs inhibit noradrenaline uptake and potentiate noradrenaline chronotropic response (desipramine congruent to protriptyline greater than doxepin). Desipramine and protriptyline, at concentrations of 10(-7) -- 10(-6)M stimulate the spontaneous rate; higher concentrations (greater than 10(-6)M) depress it. Doxepin has only a negative chronotropic effect. When the drugs are removed from the incubation medium, the depressing effect starts to disappear immediately for doxepin and desipramine and after 20 min for protriptyline. On the contrary the stimulating effect persists after repeatedly washing the preparations. Desipramine, protriptyline and doxepin extensively accumulate in the myocardial tissue (desipramine larger than or equal to protriptyline greater than doxepin). In the efflux studies doxepin is washed out more rapidly than desipramine and protriptyline. Although the kinetics of uptake and efflux of the three compounds are not sufficient to interpret their different pharmacological activities in isolated atria, they give useful information on the persistance of the sympathomimetic effect and the rapid disappearing of the negative chronotropic effect after washing.


Corticosteroid injection for coccydynia: a review of 241 patients.
We aimed to establish the short- and long-term efficacy of corticosteroid injection for coccydynia, and to determine if betamethasone or triamcinolone has the best effect. During 2009 to 2016, we treated 277 patients with chronic coccydynia with either one 6 mg betamethasone or one 20 mg triamcinolone cortisone injection. A susequent injection was given to 62 (26%) of the patients. All were reviewed three to four months after injection, and 241 replied to a questionnaire a mean of 36 months (12 to 88) after the last injection. No pain at the early review was considered early success. When the patient had not been subsequently operated on, and indicated on the questionnaire that they were either well or much better, it was considered a long-term success. At the three- to four-month review, 22 (9%) reported that they had no pain. The long-term success of one injection was 15% and rose to 29% after a second injection. Logistic regression tests showed that both early success (odds ratio (OR) 5.5, 95% confidence interval (CI) 2.1 to 14.4; p = 0.001) and late success (OR 3.7, 95% CI 1.7 to 8.3; p = 0.001) was greater with triamcinolone than with betamethasone. Late success was greater for patients with symptoms for less than 12 months (OR 3.0, 95% CI 1.4 to 6.7; p = 0.006). We saw no complications of the injections. We conclude that the effect of corticosteroid injection for coccygodynia is moderate, possibly because we used modest doses of the drugs. Even so, they seem worthwhile as they are easily and quickly performed, and complications are rare. If the choice is between injections of betamethasone or triamcinolone, the latter should be selected.Cite this article: Bone Joint Open 2020;1-11:709-714.


Role of preoperative selective portal vein embolization in two-step curative hepatectomy for hepatocellular carcinoma.
To determine the feasibility and role of ultrasound-guided preoperative selective portal vein embolization (POSPVE) in the two-step hepatectomy of patients with advanced primary hepatocellular carcinoma (HCC). Fifty patients with advanced HCC who were not suitable for curative hepatectomy were treated by ultrasound-guided percutaneous transhepatic POSPVE with fine needles. The successful rate, side effects and complications of POSPVE, changes of hepatic lobe volume and two-step curative hepatectomy rate after POSPVE were observed. POSPVE was successfully performed in 47 (94.0 %) patients. In patients whose right portal vein branches were embolized, their right hepatic volume decreased and left hepatic volume increased gradually. The ratio of right hepatic volume to total hepatic volume decreased from 62.4 % before POSPVE to 60.5 %, 57.2 % and 52.8 % after 1, 2 and 3 weeks respectively. The side effects included different degree of pain in liver area (38 cases), slight fever (27 cases), nausea and vomiting (9 cases). The level of aspartate alanine transaminase (AST), alanine transaminase (ALT) and total bilirubin (TBIL) increased after POSPVE, but returned to preoperative level in 1 week. After 2-4 weeks, two-step curative hepatectomy for HCC was successfully performed on 23 (52.3 %) patients. There were no such severe complications as ectopic embolization, local hemorrhage and bile leakage. Ultrasound-guided percutaneous transhepatic POSPVE with fine needles is feasible and safe. It can extend the indications of curative hepatectomy of HCC, and increase the safety of hepatectomy.


A bottom up approach to on-road CO2 emissions estimates: improved spatial accuracy and applications for regional planning.
On-road transportation is responsible for 28% of all U.S. fossil-fuel CO2 emissions. Mapping vehicle emissions at regional scales is challenging due to data limitations. Existing emission inventories use spatial proxies such as population and road density to downscale national or state-level data. Such procedures introduce errors where the proxy variables and actual emissions are weakly correlated, and limit analysis of the relationship between emissions and demographic trends at local scales. We develop an on-road emission inventory product for Massachusetts-based on roadway-level traffic data obtained from the Highway Performance Monitoring System (HPMS). We provide annual estimates of on-road CO2 emissions at a 1 × 1 km grid scale for the years 1980 through 2008. We compared our results with on-road emissions estimates from the Emissions Database for Global Atmospheric Research (EDGAR), with the Vulcan Product, and with estimates derived from state fuel consumption statistics reported by the Federal Highway Administration (FHWA). Our model differs from FHWA estimates by less than 8.5% on average, and is within 5% of Vulcan estimates. We found that EDGAR estimates systematically exceed FHWA by an average of 22.8%. Panel regression analysis of per-mile CO2 emissions on population density at the town scale shows a statistically significant correlation that varies systematically in sign and magnitude as population density increases. Population density has a positive correlation with per-mile CO2 emissions for densities below 2000 persons km(-2), above which increasing density correlates negatively with per-mile emissions.


Comparative genomic analysis of novel conserved peptide upstream open reading frames in Drosophila melanogaster and other dipteran species.
Upstream open reading frames (uORFs) are elements found in the 5'-region of an mRNA transcript, capable of regulating protein production of the largest, or major ORF (mORF), and impacting organismal development and growth in fungi, plants, and animals. In Drosophila, approximately 40% of transcripts contain upstream start codons (uAUGs) but there is little evidence that these are translated and affect their associated mORF. Analyzing 19,389 Drosophila melanogaster transcript annotations and 666,153 dipteran EST sequences we have identified 44 putative conserved peptide uORFs (CPuORFs) in Drosophila melanogaster that show evidence of negative selection, and therefore are likely to be translated. Transcripts with CPuORFs constitute approximately 0.3% of the total number of transcripts, a similar frequency to the Arabidopsis genome, and have a mean length of 70 amino acids, much larger than the mean length of plant CPuORFs (40 amino acids). There is a statistically significant clustering of CPuORFs at cytological band 57 (p = 10-5), a phenomenon that has never been described for uORFs. Based on GO term and Interpro domain analyses, genes in the uORF dataset show a higher frequency of ORFs implicated in mitochondrial import than the genome-wide frequency (p < 0.01) as well as methyltransferases (p < 0.02). Based on these data, it is clear that Drosophila contain putative CPuORFs at frequencies similar to those found in plants. They are distinguished, however, by the type of mORF they tend to associate with, Drosophila CPuORFs preferentially occurring in transcripts encoding mitochondrial proteins and methyltransferases. This provides a basis for the study of CPuORFs and their putative regulatory role in mitochondrial function and disease.


Sinensetin Induces Autophagic Cell Death through p53-Related AMPK/mTOR Signaling in Hepatocellular Carcinoma HepG2 Cells.
Sinensetin (SIN) has been reported to exhibit anti-inflammatory and anti-cancer activity. However, the cellular and molecular mechanism by which SIN promotes hepatocellular carcinoma (HCC) cell death remains unclear. In the present study, we investigated the induction of cell death by SIN and its underlying mechanism in HepG2 cells, an HCC cell line. We found that SIN significantly induced cell death in HepG2 cells, whereas the proliferation rate of Thle2, human liver epithelial cells, was unaffected by SIN. SIN-treated HepG2 cells were not affected by apoptotic cell death; instead, autophagic cell death was induced through the p53-mediated AMPK/mTOR signaling pathway. Inhibition of p53 degradation led to both autophagy and apoptosis in HepG2 cells. p53 translocation led to SIN-induced autophagy, whereas p53 translocation inhibited SIN-induced apoptosis. However, SIN showed apoptosis in the p53-mutant Hep3B cell line. Molecular docking simulation of the p53 core domain showed effective binding with SIN, which was found significant compared with the known p53 activator, RITA. Collectively, these data suggest that SIN may be a potential anti-cancer agent targeting autophagic cell death in human liver cancer.


Cognitive Bias for Learning Speech Sounds From a Continuous Signal Space Seems Nonlinguistic.
When learning language, humans have a tendency to produce more extreme distributions of speech sounds than those observed most frequently: In rapid, casual speech, vowel sounds are centralized, yet cross-linguistically, peripheral vowels occur almost universally. We investigate whether adults' generalization behavior reveals selective pressure for communication when they learn skewed distributions of speech-like sounds from a continuous signal space. The domain-specific hypothesis predicts that the emergence of sound categories is driven by a cognitive bias to make these categories maximally distinct, resulting in more skewed distributions in participants' reproductions. However, our participants showed more centered distributions, which goes against this hypothesis, indicating that there are no strong innate linguistic biases that affect learning these speech-like sounds. The centralization behavior can be explained by a lack of communicative pressure to maintain categories.


Equations and calculations for fermentations of butyric acid bacteria.
A stoichiometric equation has been derived which describes the interrelations among the various products and biomass in fermentations of butyric acid bacteria. The derivation of the equation is based on an assumed ATP yield, two biological regularities, and the biochemistry of product formation of the fermentations. The equation obeys the constraints imposed on growth and product formation by thermodynamics and the biochemical topology. The validity of the equation is tested using a variety of fermentation data from the literature. The uses, improvements, limitations, and extensions of the equation are also discussed in detail. For example, the fermentation equation is used to calculate the maximal possible yields of the main fermentation products.


COVID-19 Significantly Impacted Hospital Length of Stay and Discharge Patterns for Adult Spinal Deformity Patients.
Retrospective review. The primary aim was to compare length of stay (LOS) and discharge disposition of adult spinal deformity (ASD) patients undergoing surgery before and during the pandemic. Secondary aims were to compare the rates of 30-day complications, reoperations, readmissions, and unplanned emergency department (ED) visits. ASD patients often require extended LOS and non-routine discharge. Given resource limitations during the Coronavirus Disease 2019 (COVID-19) pandemic and caution regarding hospital stays, surgeons modified standard postoperative protocols to minimize patient exposure. We identified all patients who underwent elective thoracolumbar ASD surgery with more than or equal to five levels fusion at a tertiary care center during two distinct time intervals: July to December 2019 (Pre-COVID, N = 60) and July to December 2020 (During-COVID, N = 57). Outcome measures included LOS and discharge disposition (home vs. non-home), as well as 30-day major complications, reoperations, readmissions, and ED visits. Regression analyses controlled for demographic and surgical factors. Patients who underwent ASD surgery during the pandemic were younger (61 vs. 67 yrs) and had longer fusion constructs (nine vs. eight levels) compared with before the pandemic (P < 0.05 for both). On bivariate analysis, patients undergoing surgery during the pandemic had shorter LOS (6 vs. 9 days) and were more likely to be discharged home (70% vs. 28%) (P < 0.05 for both). After controlling for age and levels fused on multivariable regression, patients who had surgery during the pandemic had shorter LOS (IRR = 0.83, P = 0.015) and greater odds of home discharge (odds ratios [OR] = 7.2, P < 0.001). Notably, there were no differences in major complications, reoperations, readmissions, or ED visits between the two groups. During the COVID-19 pandemic, LOS for patients undergoing thoracolumbar ASD surgery decreased, and more patients were discharged home without adversely affecting complication or readmission rates. Lessons learned during the pandemic may help improve resource utilization without negatively influencing short-term outcomes.Level of Evidence: 3.


Closing the Care Gap: Management of Alcohol Use Disorder in Patients with Alcohol-associated Liver Disease.
Alcohol-associated liver disease (ALD)-related morbidity and mortality are rising in the United States. Although effective medications and behavioral interventions are available for the treatment of patients with alcohol use disorder (AUD), patients with ALD are profoundly undertreated for AUD. This article reviews the management of AUD in patients with ALD, with a focus on appropriate screening and diagnosis, management of alcohol withdrawal syndrome, pharmacotherapy for AUD, alcohol biomarkers, and behavioral interventions. Expanding access to AUD treatment is imperative for improving health outcomes in patients with ALD.


Microsatellite instability and mutation analysis of hMSH2 and hMLH1 in patients with sporadic, familial and hereditary colorectal cancer.
To date, at least four genes involved in DNA mismatch repair, hMSH2, hMLH1, hPMS1 and hPMS2, have been demonstrated to be altered in the germline of patients with hereditary nonpolyposis colorectal cancer (HNPCC). Additionally, defective mismatch repair is thought to account for the observation of microsatellite instability (MIN) in tumors from these patients. The genetic defect responsible for the MIN+ phenotype in sporadic colorectal cancer, however, has yet to be clearly delineated. In order to better understand the role of somatic and germline alterations within hMSH2 and hMLH1 in the process of colorectal tumorigenesis, we examined the entire coding regions of both of these genes in seven patients with MIN+ sporadic colorectal cancer, 19 patients with familial colorectal cancer, and 20 patients meeting the strict Amsterdam criteria for HNPCC. Thirteen germline, two somatic, and four neutral alterations were identified. The two somatic mutations occurred in patients having familial cancer, while the germline mutations were distributed among one sporadic (14%), three familial (16%), and nine HNPCC (45%) cases. All patients with identified mutations in the mismatch repair genes, whose tumors were available for analysis, demonstrated MIN. On the other hand, we could not identify mutations in the subset of clinically defined HNPCC patients with MIN negative tumors nor in the majority (6/7) of MIN+ sporadic tumors.


Impact of reduced tobacco smoking on lung cancer mortality in the United States during 1975-2000.
Considerable effort has been expended on tobacco control strategies in the United States since the mid-1950s. However, we have little quantitative information on how changes in smoking behaviors have impacted lung cancer mortality. We quantified the cumulative impact of changes in smoking behaviors that started in the mid-1950s on lung cancer mortality in the United States over the period 1975-2000. A consortium of six groups of investigators used common inputs consisting of simulated cohort-wise smoking histories for the birth cohorts of 1890 through 1970 and independent models to estimate the number of US lung cancer deaths averted during 1975-2000 as a result of changes in smoking behavior that began in the mid-1950s. We also estimated the number of deaths that could have been averted had tobacco control been completely effective in eliminating smoking after the Surgeon General's first report on Smoking and Health in 1964. Approximately 795,851 US lung cancer deaths were averted during the period 1975-2000: 552,574 among men and 243,277 among women. In the year 2000 alone, approximately 70,218 lung cancer deaths were averted: 44,135 among men and 26,083 among women. However, these numbers are estimated to represent approximately 32% of lung cancer deaths that could have potentially been averted during the period 1975-2000, 38% of the lung cancer deaths that could have been averted in 1991-2000, and 44% of lung cancer deaths that could have been averted in 2000. Our results reflect the cumulative impact of changes in smoking behavior since the 1950s. Despite a large impact of changing smoking behaviors on lung cancer deaths, lung cancer remains a major public health problem. Continued efforts at tobacco control are critical to further reduce the burden of this disease.


A highly sensitive fluorescent indicator dye for calcium imaging of neural activity in vitro and in vivo.
Calcium imaging of individual neurons is widely used for monitoring their activity in vitro and in vivo. Synthetic fluorescent calcium indicator dyes are commonly used, but the resulting calcium signals sometimes suffer from a low signal-to-noise ratio (SNR). Therefore, it is difficult to detect signals caused by single action potentials (APs) particularly from neurons in vivo. Here we showed that a recently developed calcium indicator dye, Cal-520, is sufficiently sensitive to reliably detect single APs both in vitro and in vivo. In neocortical neurons, calcium signals were linearly correlated with the number of APs, and the SNR was > 6 for in vitro slice preparations and > 1.6 for in vivo anesthetised mice. In cerebellar Purkinje cells, dendritic calcium transients evoked by climbing fiber inputs were clearly observed in anesthetised mice with a high SNR and fast decay time. These characteristics of Cal-520 are a great advantage over those of Oregon Green BAPTA-1, the most commonly used calcium indicator dye, for monitoring the activity of individual neurons both in vitro and in vivo.


The shifts of sediment microbial community phylogenetic and functional structures during chromium (VI) reduction.
The Lanzhou reach of the Yellow River, located at the upstream of Lanzhou, has been contaminated by heavy metals and polycyclic aromatic hydrocarbons over a long-time. We hypothesized that indigenous microbial communities would remediate those contaminants and some unique populations could play an important role in this process. In this study, we investigated the sediment microbial community structure and function from the Lanzhou reach. Sediment samples were collected from two nearby sites (site A and site B) in the Lanzhou reach along the Yellow River. Sediment geochemical property data showed that site A sediment samples contained significantly (p < 0.05) higher heavy metals than site B, such as chromium (Cr), manganese (Mn), and copper (Cu). Both site A and B samples were incubated with or without hexavalent chromium (Cr (VI)) for 30 days in the laboratory, and Cr (VI) reduction was only observed in site A sediment samples. After incubation, MiSeq sequencing of 16S rRNA gene amplicons revealed that the phylogenetic composition and structure of microbial communities changed in both samples, and especially Proteobacteria, as the most abundant phylum increased from 45.1 % to 68.2 % in site A, and 50.1 % to 71.3 % in site B, respectively. Some unique OTUs and populations affiliated with Geobacter, Clostridium, Desulfosporosinus and Desulfosporosinus might be involved in Cr (VI) reduction in site A. Furthermore, GeoChip 4.0 (a comprehensive functional gene array) data showed that genes involved in carbon and nitrogen cycling and metal resistance significantly (p < 0.05) increased in site A sediment samples. All the results indicated that indigenous sediment microbial communities might be able to remediate contaminants like Cr (VI), and this information provides possible strategies for future bioremediation of the Lanzhou reach.


Nonsteroidal anti-inflammatory drug use is associated with cancer risk reduction in chronic dialysis patients.
Previous studies have shown that nonsteroidal anti-inflammatory drug (NSAID) use might be associated with a lower risk of developing cancer in the general population. Patients on dialysis have increased risk for cancer, but there are no studies to determine the relationship between NSAID use and cancer risk in these patients. To identify any association between NSAID use and cancer risk in patients with end-stage renal disease on dialysis, we used Taiwan's National Health Insurance database to conduct a nationwide population-based, propensity score-matched cohort study. All cancers between groups were compared by Cox proportional hazards models. Compared to nonuse of NSAIDs, the use of non-COX-2-selective inhibitors (hazard ratio 0.81, 95% confidence interval 0.67-0.97) or COX-2-selective inhibitors (0.78, 0.62-0.98) was associated with a lower risk of developing cancer. NSAID use reduced the risk of respiratory (0.39, 0.19-0.79), breast (0.41, 0.19-0.89), kidney (0.58, 0.38-0.88), digestive tract (0.64, 0.49-0.85), and bladder cancers (0.73, 0.55-0.96). NSAID use, however, significantly increased risk for upper gastrointestinal bleeding (odds ratio, 1.15, 1.07-1.23) but not adverse cardiac or cerebrovascular events. Thus, NSAID use was associated with a lower risk of developing cancer in chronic dialysis patients; however, they should still be used with caution due to the side effects of gastrointestinal bleeding.


[Our strategy in the therapy of myasthenia gravis].
Surgical treatment of myasthenia gravis has at the 3 (rd) Department of Surgery, 1 (st) Medicine Faculty of Charles University in Prague a multiyear tradition which has originated in the 60's of the 20 (th) century. Since that time we carried out over 1 000 operations on the thymus, especially thymectomy for myasthenia gravis (MG) and with lesser frequency for thymomas. Thymectomy combined with exenteration of fatty tissue from the front mediastinum belongs to basic MG surgery. According to our experience an optimal approach to the thymus is given by partial sternotomy. A jugular approach is not regarded as enough radical. Videothoracoscopic approach and operation are possible but take more time, however they are the method of choice at some workplaces. The combined conservative and surgical treatment brings in 80 % of the cases an obvious improvement or deletion of the symptoms of the disease.


A sequence motif distinct from Hox binding sites controls the specificity of a Hox response element.
Hox transcription factors, in combination with cofactors such as PBC proteins, provide diverse developmental fates to cells on the anteroposterior body axis of animal embryos. However, the mechanisms by which the different Hox proteins and their cofactors generate those diverse fates remain unclear. Recent findings have provided support for a model where the DNA binding sites that directly interact with Hox-PBC heterodimers determine which member of the Hox protein family occupies and thereby regulates a given target element. In the experiments reported here, we test the function of chimeric Hox response elements and, surprisingly, find evidence that runs counter to this view. A 21 bp cofactor binding sequence from an embryonic Deformed Hox response element, containing no Hox or Hox-PBC binding sites, was combined with single or multimeric sites that bind heterodimers of Labial-type Hox and PBC proteins. Normally, multimerized Labial-PBC binding sites are sufficient to trigger a Labial-specific activation response in either Drosophila or mouse embryos. Here we find that the 21 bp sequence element plays an important role in Deformed specificity, as it is capable of switching a Labial-PBC binding site/response element to a Deformed response element. Thus, cofactor binding sites that are separate and distinct from homeodomain binding sites can dictate the regulatory specificity of a Hox response element.


Piezoelectric and pyroelectric properties of PZT/P(VDF-TrFE) composites with constituent phases poled in parallel or antiparallel directions.
Composites of lead zirconate titanate (PZT) powder dispersed in a vinylidene fluoride-trifluoroethylene copolymer [P(VDF-TrFE)] matrix have been prepared by compression molding. Three groups of polarized samples have been prepared by poling: only the ceramic phase, the ceramic and polymer phases in parallel directions, and the two phases in antiparallel directions. The measured permittivities of the unpoled composites are consistent with the predictions of the Bruggeman model. The changes in the pyroelectric and piezoelectric coefficients of the poled composites with increasing ceramic volume fraction can be described by modified linear mixture rules. When the ceramic and copolymer phases are poled in the same direction, their pyroelectric activities reinforce while their piezoelectric activities partially cancel. However, when the ceramic and copolymer phases are poled in opposite directions, their piezoelectric activities reinforce while their pyroelectric activities partially cancel.


Genetic code and metabolism: The perpetual waltz.
Since the origin of life, metabolism and protein synthesis have evolved together to balance the vast amounts of ATP and amino acids required for genetic translation with the rest of the cell's energy needs. A new study offers satisfying insights into a long-standing evolutionary mystery surrounding a fused, bifunctional aminoacyl-tRNA synthetase. To avoid depleting cells from an essential amino acid generated by the Krebs cycle, harvesting for Glu and Pro by the translation machinery was unified in animals, thus preventing a Pro-hungry translational apparatus from depleting the cell of essential Glu reserves.


Dehydropyrrolizidine alkaloids, including monoesters with an unusual esterifying acid, from cultivated Crotalaria juncea (Sunn Hemp cv.'Tropic Sun').
Cultivation of Crotalaria juncea L. (Sunn Hemp cv. 'Tropic Sun') is recommended as a green manure crop in a rotation cycle to improve soil condition, help control erosion, suppress weeds, and reduce soil nematodes. Because C. juncea belongs to a genus that is known for the production of toxic dehydropyrrolizidine alkaloids, extracts of the roots, stems, leaves, and seeds of 'Tropic Sun' were analyzed for their presence using HPLC-ESI/MS. Qualitative analysis identified previously unknown alkaloids as major components along with the expected macrocyclic dehydropyrrolizidine alkaloid diesters, junceine and trichodesmine. The dehydropyrrolizidine alkaloids occurred mainly as the N-oxides in the roots, stems, and, to a lesser extent, leaves, but mainly as the free bases in the seeds. Comprehensive spectrometric and spectroscopic analysis enabled elucidation of the unknown alkaloids as diastereoisomers of isohemijunceine, a monoester of retronecine with an unusual necic acid. The dehydropyrrolizidine alkaloid contents of the roots, stems, and leaves of immature plants were estimated to be 0.05, 0.12, and 0.01% w/w, respectively, whereas seeds were estimated to contain 0.15% w/w.


Bridged-bowtie and cross bridged-bowtie nanohole arrays as SERS substrates with hotspot tunability and multi-wavelength SERS response.
In this paper, we present bridged-bowtie nanohole arrays and cross bridged-bowtie nanohole arrays in a gold thin film as surface enhanced Raman scattering (SERS) substrates. These SERS substrates not only exhibit large electromagnetic enhancement of SERS but also have the SERS enhancement spread over a much larger area than what could be present in SERS substrates consisting of nanopillar arrays or nanopillar plasmonic nanoantennas. Numerical simulations based on the finite difference time domain (FDTD) method are employed to determine electric field enhancement factors (EFs) and therefore the electromagnetic SERS enhancement factor for these SERS substrates. It was observed that bridged-bowtie nanohole arrays and cross bridge-bowtie nanohole arrays exhibit a highest electromagnetic SERS enhancement factor (EF) of ~109, which is orders of magnitude higher than what has been previously reported for nanohole arrays as SERS substrates. This electromagnetic SERS EF (of ~109) is spread over a hotspot region of ~100 nm2 (in each periodic unit of the array), which is larger than the case of nanopillar arrays. In addition, it was observed that an electromagnetic SERS enhancement factor of at least 108 is spread over a large area (500 nm2 in each periodic unit of the array), thus increasing the average enhancement factor. It was observed that the bridged-bowtie nanohole arrays and the cross bridged-bowtie nanohole arrays can be employed as effective SERS substrates in both the transmission mode and the reflection mode. The resonance wavelength of these arrays of nanoholes can be tuned by altering the size of the nanoholes. The effects of varying the gold film thickness and the diameter of the bridged-bowtie nanoholes forming the arrays were also analyzed. The bridged-bowtie nanohole arrays and cross bridged-bowtie nanohole arrays exhibit very high electric field enhancement factors (EFs) at more than one wavelength, and can therefore be used to obtain a multi-wavelength SERS response. Moreover, the cross bridged-bowtie nanohole array allows the tunability of the position of the hotspot with the rotation of the direction of the polarization of incident field.


Prevention of Clostridium difficile spore formation by sub-inhibitory concentrations of tigecycline and piperacillin/tazobactam.
Sporulation of Clostridium difficile during infection and persistence of spores within the gut could partly explain treatment failures and recurrence. However, the influence of antibiotics on sporulation is unclear. The objective of our study was to evaluate the impact of ciprofloxacin, metronidazole, piperacillin/tazobactam, tigecycline, and vancomycin on C. difficile sporulation in vitro. The reference strains ATCC 9689, 630, VPI 10463, and seven other clinical isolates of C. difficile were used, including three epidemic NAP1/027 isolates. Minimum inhibitory concentrations (MIC) were determined and sporulation was assessed after growth in the absence or presence of ≤0.5x MIC concentrations of each antibiotic. All strains were sensitive to the antibiotics tested, except ribotype 027 isolates that were resistant to ciprofloxacin (MIC = 128 mg/L). Metronidazole and vancomycin generally did not significantly affect spore production in C. difficile, although vancomycin slightly affected sporulation of a few isolates. Ciprofloxacin inhibited sporulation of ribotype 027 isolates mainly. Interestingly, sub-MIC concentrations of piperacillin/tazobactam reduced spore formation in several isolates. However, the most striking observation was made with tigecycline, with an important reduction of spore formation in most isolates. The capacity of C. difficile to sporulate can be significantly affected by certain antibiotics. The reduced sporulation observed with tigecycline and piperacillin/tazobactam might explain why these antibiotics are generally associated with lower risk of C. difficile infections. In addition, the inhibition of sporulation might partly explain the apparent efficacy of tigecycline for treatment of patients with recurrent infection.


Clinical practice in COVID-19: The most frequently asked questions to infectious diseases specialists.
Since the emergence of the disease caused by the severe respiratory syndrome coronavirus 2 (SARS-CoV-2) - COVID-19 - in late December 2019, a vast number of publications on the subject appeared in peer-reviewed journals and preprints. Despite the significant amount of available information, infectious disease physicians are requested to solve questions from colleagues, patients, and relatives on a daily basis. Here, we aim to describe the evidence supporting the answers for frequently asked questions, based on a literature review. We created a web-based questionnaire which was distributed to a group of 70 infectious disease specialists and medical residents, asking what questions and issues they most frequently faced. The 10 most frequent questions guided the topics for a narrative review. We provide evidence and consensus-based information on subjects such as infection and transmission, isolation, management of COVID-19 confirmed cases, reinfection, clinical-therapeutic management, vaccination, and antibodies post-infection/vaccination. Correctly clarifying doubts and providing clear information to physicians, patients, and family members helps to better manage COVID-19 in the community and the hospital settings.


Cardiothoracic Magnetic Resonance Angiography.
Catheter-based angiography is regarded as the clinical reference imaging technique for vessel imaging; however, it is invasive and is currently used for intervention or physiologic measurements. Contrast enhanced magnetic resonance angiography (MRA) with gadolinium-based contrast agents can be performed as a three-dimensional (3D) MRA or as a time resolved 3D (4D) MRA without physiologic synchronization, in which case cardiac and respiratory motion may blur the edges of the vessels and cardiac chambers. Ferumoxytol has recently been a popular contrast agent for MRA in patients with chronic renal failure. Noncontrast 3D MRA with ECG gating and respiratory navigation are safe and accurate noninvasive cross-sectional imaging techniques for the visualization of great vessels of the heart and coronary arteries in a variety of cardiovascular disorders including complex congenital heart diseases. Noncontrast flow dependent MRA techniques such as time of flight, phase contrast, and black-blood MRA techniques can be used as complementary or primary techniques. Here we review both conventional and relatively new contrast enhanced and non-contrast enhanced MRA techniques including ferumoxytol enhanced MRA, and bright-blood and water-fat separation based noncontrast 3D MRA techniques.


The Effect of Surgery on the Prognosis of Gastric Lymphoma: A Meta-analysis.
Surgery is an effective clinical approach that has been used for the treatment of gastric lymphoma. However, its specific effect on the prognosis of patients with gastric lymphoma remains largely unknown. The current meta-analysis aimed to identify the effect of surgery on the prognosis of gastric lymphoma. We searched the MEDLINE, Embase, and Cochrane Central databases to obtain relevant studies investigating the influence of surgery on overall survival (OS) and relapse-free survival (RFS). We extracted the hazard ratios (HRs) and associated 95% confidence intervals (CIs) of each included report for pooled analysis. We assessed heterogeneity (I2 statistic) and funnel plots to select the data models and evaluate publication bias. Ultimately, we included 12 studies containing 26 comparisons in the current quantitative meta-analysis. The analysis revealed that surgery had no significant effect on OS (HR .83, P = .13) or RFS (HR .78, P = .08). However, subgroup analysis revealed that the effect of surgery on OS differed significantly between the surgery plus conservative therapy subgroup and the conservative therapy alone groups, with HR = .69 (P = .01). No significant publication bias was detected regarding the main outcomes. Surgery had a limited effect on the prognosis of patients with gastric lymphoma. However, the use of surgery as an additional therapy may confer potential benefits. This was an interesting research direction, and additional high-quality, large-scale randomized controlled trials should be conducted.


Shared Decision-Making in Emergency Departments: Context Sensitivity Through Divergent Discourses.
Patient-centred care and the empowerment of patients through shared clinical decision-making is a key goal of healthcare systems internationally. The Emergency Department is one of the first opportunities for shared decision-making to occur, with information exchanged between patient and clinician, between clinical disciplines, across the continuum of care, and between clinicians and ancillary departments including radiology and pathology laboratories. The successful development and implementation of sustainable health information technology (HIT) to support shared decision-making in Emergency care requires an understanding of the factors affecting this context. From a purposive, maximum variation sample of clinicians and a convenience sample of patients across three metropolitan and regional Emergency Departments in Australia, we identified three divergent discourses from an in-depth qualitative exploration of issues around shared decision-making. This allowed us to identify unanticipated factors affecting patient-centred care to inform context-sensitive implementation of HIT in the Emergency Department.


The Good Food for Learning Universal Curriculum-Integrated Healthy School Lunch Intervention: Protocol for a Two-Year Matched Control Pre-Post and Case Study.
Good nutrition affects children's health, well-being, and learning, and schools offer an important setting to promote healthy behaviors that can last a lifetime. Once children reach school age, they spend more of their waking hours in school than in any other environment. Children's eating habits may be easier to influence than those of adults. In Canada, households with children are more likely to experience food insecurity, and school food programs that are universally available to all children can support the development of healthy eating patterns across groups of varying socioeconomic status. There is a significant gap in the rigorous community-engaged academic research on the impact of school meal programs, especially universal ones. The aim of this population health intervention research is to study the impact of a 2-year universal, curriculum-integrated healthy school lunch program in elementary schools in Saskatoon, Saskatchewan, Canada, on food consumption, dietary quality and food and nutrition-related knowledge, attitudes, and practices. This population health intervention study will be conducted in 2 intervention elementary schools matched with 2 control schools. We will collect preintervention data, including objective measurements of food eaten at school and food-related knowledge, attitudes, and behaviors. This will be followed by the intervention itself, along with qualitative case studies of the intervention process in the 2 intervention schools. Then, we will collect postintervention data similar to the preintervention data. Finally, we will finish the data analysis and complete the ongoing sharing of learning from the project. This study was funded in April 2020 but because of the COVID-19 pandemic, data collection did not begin until May 2021. The intervention will begin in September 2021 and end in June 2023, with end point data collection occurring in May and June 2023. The case study research will begin in September 2021 and will be ongoing for the duration of the intervention. The opportunity we have to systematically and comprehensively study a curriculum-integrated school lunch program, as well as the promising practices for school food programs across Canada, is without precedent. DERR1-10.2196/30899.


NR4A orphan nuclear receptors: transcriptional regulators of gene expression in metabolism and vascular biology.
Members of the nuclear hormone receptor superfamily, including the peroxisome proliferator-activated receptor and the liver X receptor subfamilies, orchestrate transcriptional networks involved in the control of metabolism and the development of vascular disease. In addition to these well-characterized ligand-activated transcription factors, the nuclear receptor (NR) superfamily comprises many orphan receptors, whose ligands and physiological functions remain unknown. Among this group of orphan receptors is the NR4A subfamily, including Nur77 (NR4A1), Nurr1 (NR4A2), and NOR1 (NR4A3). These orphan NRs constitute an evolutionary ancient and highly conserved group of transcription factors. In contrast to other members of the superfamily, NR4A receptors function as ligand-independent transcription factors and immediate- or early-response genes, which are rapidly induced by a pleiotropy of environmental cues. Early functional studies have pointed to a critical role of NR4A receptors in regulating differentiation, proliferation, and apoptosis. More recent research has characterized NR4A receptors as key transcriptional regulators of glucose and lipid homeostasis, adipogenesis, inflammation, and vascular remodeling. In this review, we will summarize recent advances in understanding the molecular biology and physiological functions of NR4A receptors and discuss their role in the transcriptional control of metabolism and vascular remodeling.


Reduced inhibition and increased output of layer II neurons in the medial entorhinal cortex in a model of temporal lobe epilepsy.
Temporal lobe epilepsy is the most common type of epilepsy in adults, and its underlying mechanisms are unclear. To investigate how the medial entorhinal cortex might contribute to temporal lobe epilepsy, we evaluated the histology and electrophysiology of slices from rats 3-7 d after an epileptogenic injury (pilocarpine-induced status epilepticus). Nissl staining, NeuN immunocytochemistry, and in situ hybridization for GAD65 mRNA were used to verify the preferential loss of glutamatergic neurons and the relative sparing of GABAergic interneurons in layer III. From slices adjacent to those that were used for anatomy, we obtained whole-cell patch recordings from layer II medial entorhinal cortical neurons. Recordings under current-clamp conditions revealed similar intrinsic electrophysiological properties (resting membrane potential, input resistance, single spike, and repetitive firing properties) to those of controls. Spontaneous IPSCs were less frequent (68% of controls), smaller in amplitude (57%), and transferred less charge (51%) than in controls. However, the frequency, amplitude, and rise time of miniature IPSCs were normal. These findings suggest that after epileptogenic injuries the layer II entorhinal cortical neurons receive less GABA(A) receptor-mediated synaptic input because presynaptic inhibitory interneurons become less active. To investigate the possible consequences of reduced spontaneous inhibitory input to layer II neurons, we recorded field potentials in the dentate gyrus, their major synaptic target. At 5 d after pilocarpine-induced status epilepticus the spontaneous field potentials recorded in vivo were over three times more frequent than in controls. These findings suggest that an epileptogenic injury reduces inhibition of layer II neurons and results in excessive synaptic input to the dentate gyrus.


Building back better: The COVID-19 pandemic and transport policy implications for a developing megacity.
The COVID-19 pandemic has affected human mobility via lockdowns, social distancing rules, home quarantines, and the full or partial suspension of transportation. Evidence-based policy recommendations are urgently needed to ensure that transport systems have resilience to future pandemic outbreaks, particularly within Global South megacities where demand for public transport is high and reduced access can exacerbate socio-economic inequalities. This study focuses on Metro Manila - a characteristic megacity that experienced one of the most stringent lockdowns worldwide. It analyzes aggregated cell phone and GPS data from Google and Apple that provide a comprehensive representation of mobility behavior before and during the lockdown. While significant decreases are observed for all transport modes, public transport experienced the largest drop (-74.5 %, on average). The study demonstrates that: (i) those most reliant on public transport were disproportionately affected by lockdowns; (ii) public transport was unable to fulfil its role as public service; and, (iii) this drove a paradigm shift towards active mobility. Moving forwards, in the short-term policymakers must promote active mobility and prioritize public transport to reduce unequal access to transport. Longer-term, policymakers must leverage the increased active transport to encourage modal shift via infrastructure investment, and better utilize big data to support decision-making.


A novel and efficient immunoglobulin Y extraction method using poloxamer-polyethylene glycol.
Although many IgY extraction methods (such as polyethylene glycol (PEG) precipitation method, octanoic acid method, water dilution method, etc.) have been established, there is still industrial drive and real need in developing scale-up IgY production methods. Some previous studies have reported that poloxamer degreasing method shows very good result in IgY extraction from egg yolk with high degreasing speed, harmlessness, simpleness in operation and minimal effect on antibody titer. In this study, we developed a new method, poloxamer-PEG method, to obtain functional IgY with high purity and yield. First, the delipidation solution was added into the diluted yolk samples, and then the filtrates were collected from the diluted yolk samples after 3 hr in room temperature. PEG-6000 was added into the collected filtrates and the mixture was centrifuged after shaking on the roller mixer for 45 min at room temperature. Last, the precipitates were resuspended in 1 mL phosphate buffered solution (PBS) buffer and dialyzed overnight. The results showed that the total protein concentrate of extractive could reach at 30 mg/mL and the purity of the IgY could reach at 92.71% with the novel method, which was superior to the PEG precipitation method and water dilution method.


Design of alveolate Se-inserted TiO2 and its effect on osteosarcoma cells and osteoblasts.
Osteosarcoma is a common clinical disease with high incidence, relapse rate and lethality. Thus it is urgently necessary to fabricate bone implants with anti-tumor functions to improve the prognosis of bone cancer. In this study, a novel double-layer TiO2 nano-grid with an outer diameter of 100 nm and an inner diameter of 35 nm is prepared by a simple two-step anodization procedure. In the outer pore of the double-layer TiO2 nano-grid, we precisely embed selenium (Se) nanoparticles using electrodeposition, and this process can be readily tailored by adjusting the time. Biological assays indicate that the prepared Se-embedded TiO2 nano-grid arrays show a dose-dependent anti-tumor effect by inducing apoptosis in MG63 cells. Compared with the Ti substrate, the Se-embedded TiO2 which has a double-layer honeycomb structure facilitates healthy cell (MC3T3-E1) growth when the electrodeposition time is less than 1 h. Thus the novel bone implants have a balanced anti-tumor effect and biocompatibility and are therefore potential candidates for the treatment of osteosarcoma.


Quantitative determination of intact glucosinolates in broccoli, broccoli sprouts, Brussels sprouts, and cauliflower by high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry.
Many methods have been proposed to analyze glucosinolates, a class of phytochemicals whose breakdown products are thought to be responsible for an improvement in health; however, few are quantitative and many are time consuming. A selective and sensitive quantitative method for direct determination of intact glucosinolates was developed using liquid chromatography coupled to electrospray ionization tandem mass spectrometry with selected reaction monitoring detection. Detection limits for glucoiberin, sinigrin, progoitrin, glucoerucin, and glucotropaeolin were 1.75, 1.38, 1.36, 0.6, and 0.63 pmol, respectively. Intraassay precision of the method was within 10% for each compound. The method was successfully applied to quantify 10 individual glucosinolates in broccoli, broccoli sprouts, Brussels sprouts, and cauliflower. The advantage of the proposed method includes analysis of individual intact glucosinolates rather than the conversion to desulfoglucosinolates, an increased selectivity through the use of mass spectrometry, and a 10-fold improvement in detection sensitivity over conventionally used HPLC techniques.


Invasive bladder cancer in the eighties: transurethral resection or cystectomy?
Describe morbidity and survival in patients older than 80 years with muscle invasive bladder cancer (MIBC) treated with radical cystectomy (RC) or transurethral resection (TUR) in our institution. We reviewed our database of all patients older than 80 years treated with RC and TUR for MIBC between 1993 and 2005 in our institution. Twenty-seven patients were submitted to RC, with mean age of 82 years and mean follow-up of 16.4 months. RC was carried out following diagnosis of previous MIBC in 14 cases (51.9%). The American Society of Anesthesiology (ASA) score was III or IV in 23 patients (85.1%). Seventy-two patients with a mean age of 84 years and mean follow-up of 33 months, diagnosed with MIBC, were managed by means of TUR. The ASA score was III-IV in 64 (88.8%) patients. Pathological stage of the RC specimen was pT3 in 18 cases (66.7%). Mean hospital stay was 16 days. Early complications were assessed in 8 patients (29.6%), with an overall survival (OS) of 42.94%, and cancer-specific survival (CSS) of 60.54%. In patients submitted to TUR, clinical stage was T2 in 36 cases (50%). The mean hospital stay was 7 days, with a readmission rate (RR) of 87.5%. OS and CSS was less than 20%. RC in octogenarian patients is a safe procedure, with complication and survival rates comparable to RC series in general population. Transurethral resection (TUR) for patients with MIBC within this age range is a much less morbid procedure, but disease specific survival is lower.


[Computer modeling of the human cytochrome P-450 2E1 complex formation].
A comparison has been made between spatial structures of human CYP2E1 obtained experimentally and those calculated using the computer methods. The structures were characterized by such parameters as total energy, protein pocket volume and total volume of molecules as well as the analysis of spatial geometry. The obtained results have proved that the model calculated and optimized by us can be used for studing the mechanisms of interaction of the active center of the enzyme with substrates and inhibitors. An assumption was made in the course of the research that one of the possible mechanisms of inactivation of the enzyme is the reduction of protein pocket volume, which prevents substrate access to the active center.


Multigenerational and Transgenerational Effects of Environmentally Relevant Concentrations of Endocrine Disruptors in an Estuarine Fish Model.
Many pollutants cause endocrine disruption in aquatic organisms. While studies of the direct effects of toxicants on exposed organisms are commonplace, little is known about the potential for toxicant exposures in a parental (F0) generation to affect unexposed F1 or F2 generations (multigenerational and transgenerational effects, respectively), particularly in estuarine fishes. To investigate this possibility, we exposed inland silversides (Menidia beryllina) to environmentally relevant (low ng/L) concentrations of ethinylestradiol, bifenthrin, trenbolone, and levonorgestrel from 8 hpf to 21 dph. We then measured development, immune response, reproduction, gene expression, and DNA methylation for two subsequent generations following the exposure. Larval exposure (F0) to each compound resulted in negative effects in the F0 and F1 generations, and for ethinylestradiol and levonorgestrel, the F2 also. The specific endpoints that were responsive to exposure in each generation varied, but included increased incidence of larval deformities, reduced larval growth and survival, impaired immune function, skewed sex ratios, ovarian atresia, reduced egg production, and altered gene expression. Additionally, exposed fish exhibited differences in DNA methylation in selected genes, across all three generations, indicating epigenetic transfer of effects. These findings suggest that assessments across multiple generations are key to determining the full magnitude of adverse effects from contaminant exposure in early life.


Central Metabolism Is Tuned to the Availability of Oxygen in Developing Melon Fruit.
Respiration of bulky plant organs such as fleshy fruits depends on oxygen (O2) availability and often decreases with O2 concentration to avoid anoxia, but the relationship between O2 diffusional resistance and metabolic adjustments remains unclear. Melon fruit (Cucumis melo L.) was used to study relationships between O2 availability and metabolism in fleshy fruits. Enzyme activities, primary metabolites and O2 partial pressure were quantified from the periphery to the inner fruit mesocarp, at three stages of development. Hypoxia was gradually established during fruit development, but there was no strong oxygen gradient between the outer- and the inner mesocarp. These trends were confirmed by a mathematical modeling approach combining O2 diffusion equations and O2 demand estimates of the mesocarp tissue. A multivariate analysis of metabolites, enzyme activities, O2 demand and concentration reveals that metabolite gradients and enzyme capacities observed in melon fruits reflect continuous metabolic adjustments thus ensuring a timely maturation of the mesocarp. The present results suggest that the metabolic adjustments, especially the tuning of the capacity of cytochrome c oxidase (COX) to O2-availability that occurs during growth development, contribute to optimizing the O2-demand and avoiding the establishment of an O2 gradient within the flesh.


[Infant mortality due to avoidable causes in a city in Northeastern Brazil].
This is a cross-sectional study that aimed to describe the occurrence of infant mortality in Recife (PE) between 2000 and 2009, second to avoidable causes. The population composed of cases of deaths between 2000 and 2009 among the infants of mothers living in Recife. Deaths were classified as avoidable by using the List of avoidable causes of deaths resulting from interventions within the Brazilian National Health System (SUS). Descriptive statistics were used for data analysis. A decrease in the infant mortality coefficient from 20.4 to 12.1 per 1.000 live births was observed (reduction of 40.6%). From the total of 3.743 deaths registered, 2.861 (76.4%) were classified as avoidable. It was notable that 61.2% of the deaths could have been avoided through appropriate care for the woman during the pregnancy. An approach in which avoidability is analyzed may assist in discussions relating to organization, quality and access to healthcare service, and in identifying deaths that could have been avoided through appropriate mother-child healthcare.


Are en face frozen sections accurate for diagnosing margin status in melanocytic lesions?
To assess the diagnostic accuracy of margin evaluation of melanocytic lesions using en face frozen sections compared with standard paraffin-embedded sections, we studied 2 sets of lesions in which en face frozen sections were used for analysis of surgical margins (13 from malignant melanomas [MMs] and 10 from nonmelanocytic lesions [NMLs]). Routine permanent sections were cut after routine processing. The slides were mixed and coded randomly. Fifteen dermatopathologists examined the cases separately. Margin status was categorized as positive, negative, or indeterminate. Kappa statistics were calculated per dermatopathologist and per case. One case from each group was excluded because epidermis was not available in the routine sections. Of 330 evaluations (22 cases, 15 dermatopathologists), there were 132 diagnostic discrepancies (40.0%): 66 each for MM and NML (mean per case for both diagnoses, 6). In 9 instances (6.8%), the change was from positive (frozen) to negative (permanent) and in 43 (32.6%), from negative (frozen) to positive (permanent). There was poor agreement between frozen and permanent sections (kappa range per dermatopathologist, -0.1282 to 0.6615). If permanent histology is considered the "gold standard" for histologic evaluation, en face frozen sections are not suitable for accurate surgical margin assessment of melanocytic lesions.